17: Attention and frontal lobe function: Studies of neural mechanisms of age-related changes in attention and frontal lobe executive processes. Our broad, long-term objective is to increase the knowledge of how the protective effects of brain reserve allow the aging brain to maintain cognitive operations. We believe that a more complete understanding of the natural neural compensatory mechanisms that occur in the 'normal' aging process will lead to advances in the understanding and treatment of pathological conditions of aging of the brain. This project will provide data to support a longitudinal study of changes in the neural substrates of working memory in normal aging. Hypofrontality, as observed by decreased glucose metabolism in the frontal areas of the brain, is a hallmark of the aging brain. In this project we will examine how this hypofrontality affects the neural substrates of verbal working memory (VWM) in the aging brain. It is generally believed that VWM requires synergistic actions of the dorsolateral prefrontal cortex (DLPFC),the anterior cingulate gyrus (GCa), which is part of the frontal cortex, and the lateral parietal cortex (Gpi). We will test the hypothesis that there is functional plasticity within the triad of structures involved in WM that allows for compensation for the effects of aging and brain reserve. We will use a VWM task to examine the neural activation in older subjects compared to younger subjects, and older subjects with more education (OE+) compared to older subjects with less education (OE-). We will also correlate activation in WM related areas with estimated premorbid intelligence. It is hypothesized that older subjects will demonstrate a functional shift from frontal areas to posterior areas during performance of a VWM task. It is further hypothesized that OE-subjects compared to OE+ will show a functional shift from the frontal areas to the posterior areas during performance of a VWM task. Finally, it is hypothesized premorbid intellectual functioning will correlate with the frontal to posterior shift in activation during WM performance. To achieve the following specific aims we will use [15O]water-positron emission tomography (PET) to measure neural activation as a function of aging and brain reserve capacity during performance of a VWM task. The first specific aim will test the hypothesis that older subjects show less activation in the GCa and DLPFC and increased activation in the GPi during VWM compared to younger subjects as a result of the functional shift from anterior to the posterior aspects of the WM triad. The second specific aim will test the hypothesis that OE-compared to OE+ subjects will show less activation in the GCa and DLPFC and increased compensatory activation in the GPi as a result of the functional shift from anterior to posterior aspects of the WM system. The third specific aim will test the hypothesis that there is a positive relationship between activation in the DLPFC and GCa with estimated premorbid intelligence and an inverse relationship between activation in the GPi with estimated premorbid intelligence during WM performance.